Palmar-plantar erythrodysesthesia (PPE), also known as hand-foot syndrome (HFS), is a frequent dermatologic toxicity wherein the tissues of the palms and soles become red, painful and thickened, with possible blistering and peeling of the skin.
PPE is associated with many commonly used anticancer agents, particularly the VEGF-kinase inhibitors sorafenib (Nexevar™) and sunitinib (Sutent™), infusional 5-fluoracil (5-FU), capecitabine (Xeloda™), and liposomal doxorubicin (Doxil™). Over 400,000 patients worldwide are treated with these agents each year. PPE is among the most common reasons for dose holding, dose reduction and/or treatment discontinuation for these anti-cancer agents. The frequency of any grade (grade 1-3) PPE is up to 21% for sunitinib, 30% for sorafenib, 54% for capecitabine, and 51% for liposomal doxorubicin (1-4). The frequency of severe (grade 3) PPE is seen in up to 5% of patients for sunitinib, 8% for sorafenib, 17% for capecitabine and 24% for liposomal doxorubicin (1-7). Thus, PPE represents an important toxicity not only because of the suffering it causes directly, but also because this toxicity often limits the potential benefits of otherwise effective anti-cancer therapies.
The standard of care for the management of PPE currently includes only the use of emollients and discontinuation or dose reduction of the relevant anti-cancer treatment. More effective, mechanism based treatments for PPE are urgently needed.
The present invention overcomes previous shortcomings in the art by providing compositions and methods of treating PPE and/or drug toxicity associated reactions, disorders and/or symptoms in a subject.